Biology subjects

Vanderlip, C.

Publications and source records attributed to Vanderlip, C..

4 recordsLinked to original sources

bioRxiv2025

Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults

Age-related deficits in episodic memory and mnemonic discrimination are associated with an increased risk of neurodegenerative diseases, such as Alzheimers disease (AD) (Stark et al., 2013). While much research has focused on hippocampal contributions to these age-related changes (Stark et al., 2019), less is known about the role of posterior cingulate cortex (PCC) especially reduced inhibition in episodic memory deficit. PCC has connections to the medial temporal lobe and is linked to memory declines (Greicius et al., 2004). It is also one of the most vulnerable regions to amyloid deposition in AD (Yokoi et al., 2018). This study hypothesized and found that age-related declines in GABAergic function (brains major inhibitory neurotransmitter) within the PCC contributes to individual differences in memory performance in healthy older adults. Using Magnetic Resonance Spectroscopy, we measured GABA levels in the PCC in 22 healthy younger and 30 older adults. We assessed episodic memory using Rey Delayed Auditory Verbal Learning Test (RAVLT) and Mnemonic Similarity Task (MST). We found that both raw GABA levels and episodic memory performance are lower in older adults compared to young. This reduction in GABA levels is subserved by age-related changes in tissue-composition as evidenced by no age-group differences in corrected GABA levels. More importantly, lower GABA levels (independent of tissue-correction) were associated with poorer episodic performance including delayed recall and mnemonic discrimination. This research suggests that therapeutically targeting posterior cingulate GABA levels might help slow or alleviate memory decline. Significance StatementThis study provides novel insights into the role of posterior cingulate cortex (PCC) GABA+ levels in age-related memory deficits. Our findings demonstrate that lower PCC GABA+ levels in older adults are associated with poorer performance on episodic memory tasks, particularly those involving mnemonic discrimination and word-list learning. This research expands on the growing body of literature linking GABAergic dysfunction to age-related cognitive impairments and suggests that GABAergic changes in the PCC contribute to episodic memory deficits. Importantly, our results highlight the potential of targeting PCC GABA levels as a therapeutic strategy to slow or mitigate memory decline in aging. These findings also offer promising avenues for future research into early biomarkers for Alzheimers disease and other neurodegenerative conditions.

neuroscience↗

bioRxiv2024

Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination

Cerebral amyloid-beta (A{beta}) accumulation, a hallmark pathology of Alzheimers disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether A{beta} contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of A{beta} deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits. In this context, we tested whether specific domains of mnemonic discrimination, a neural computation essential for episodic memory, exhibit specific deficits related to early A{beta} deposition. We tested 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (A{beta}-PET), and a control group of 35 young adults, on a suite of mnemonic discrimination tasks taxing object, spatial, and temporal domains. We hypothesized that A{beta} pathology would be selectively associated with temporal discrimination performance due to A{beta}s propensity to accumulate in the basal frontotemporal cortex, which supports temporal processing. Consistent with this hypothesis, we found a dissociation in which generalized age-related deficits were found for object and spatial mnemonic discrimination, while A{beta}-PET levels were selectively associated with deficits in temporal mnemonic discrimination. Further, we found that higher A{beta}-PET levels in medial orbitofrontal and inferior temporal cortex, regions supporting temporal processing, were associated with greater temporal mnemonic discrimination deficits, pointing to the selective vulnerability of circuits related to temporal processing early in AD progression. These results suggest that A{beta} accumulation within basal frontotemporal regions may disrupt temporal mnemonic discrimination in preclinical AD, and may serve as a sensitive behavioral biomarker of emerging AD progression.

neuroscience↗

bioRxiv2024

Myo-inositol and total NAA in the hippocampus are linked to CSF tau pathology in cognitively normal older adults

INTRODUCTIONUnderstanding relationships between in vivo neurometabolic changes and Alzheimers disease (AD) pathology in the hippocampus, a region vulnerable to early changes in AD, will support early diagnosis. METHODSTwo studies using 1H-MRS examined concentrations of myo-inositol (MI), total creatine (tCr) and total NAA (tNAA) in the hippocampus. The first study compared hippocampal metabolite concentrations in healthy young and older adults and the second study assessed relationships between hippocampal metabolites and cerebrospinal fluid (CSF) measurements of A{beta}42, phosphotau 181 (pTau181), and total tau (t-Tau) while adjusting for demographic covariates and spectral characteristics (linewidth, signal- to-noise ratio) in a separate group of older adults ranging from cognitively normal (CN) to AD-dementia. RESULTSHippocampal MI, but not tCr or tNAA, was increased in cognitively normal older versus young adults. Within the second older adult group, MI and tNAA, but not tCr, were linked to increases in CSF pTau181 and t-Tau, but not A{beta}42. DISCUSSIONTau deposition in cognitively normal individuals is associated with biochemical changes related to glial reactivity and neural integrity in the hippocampus.

neuroscience↗

bioRxiv2024

Cognitive modeling of the Mnemonic Similarity Task as a digital biomarker for Alzheimer's Disease

AD related pathologies, such as beta-amyloid (A{beta}) and phosphorylated tau (pTau), are evident decades before any noticeable decline in memory occurs. Identifying individuals during this asymptomatic phase is crucial for timely intervention. The Mnemonic Similarity Task (MST), a modified recognition memory task, is especially relevant for early AD screening, as it assesses hippocampal integrity, a region affected (both directly and indirectly) early in the progression of the disease. Further, strong inferences on the underlying cognitive mechanisms that support performance on this task can be made using Bayesian cognitive modeling. We assessed whether analyzing MST performance using a cognitive model could detect subtle changes in cognitive function and AD biomarker status prior to overt cognitive decline. We analyzed MST data from >200 individuals (young, cognitively healthy older adults, and individuals with MCI), a subset of which also had existing CSF A{beta} and pTau data. Traditional performance scores and cognitive modeling using multinomial processing trees was applied to each participants MST data using Bayesian approaches. We assessed how well each could predict age group, memory ability, MCI status, A{beta}/pTau status using ROC analyses. Both approaches predicted age group membership equally, but cognitive modeling approaches exceeded traditional metrics in all other comparisons. This work establishes that cognitive modeling of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for both screening and monitoring older adults during the asymptomatic phase of AD.

neuroscience↗